Genome-Wide Transcriptomic Analysis of Intestinal Tissue to Assess the Impact of Nutrition and a Secondary Nematode Challenge in Lactating Rats

Gastrointestinal nematode infection is a major challenge to the health and welfare of mammals. Although mammals eventually acquire immunity to nematodes, this breaks down around parturition, which renders periparturient mammals susceptible to re-infection and an infection source for their offspring. Nutrient supplementation reduces the extent of periparturient parasitism, but the underlying mechanisms remain unclear. Here, we use a genome wide approach to assess the effects of protein supplementation on gene expression in the small intestine of periparturient rats following nematode re-infection.The use of a rat whole genome expression microarray (Affymetrix Gene 1.0ST) showed significant differential regulation of 91 genes in the small intestine of lactating rats, re-infected with Nippostrongylus brasiliensis compared to controls; affected functions included immune cell trafficking, cell-mediated responses and antigen presentation. Genes with a previously described role in immune response to nematodes, such as mast cell proteases, and intelectin, and others newly associated with nematode expulsion, such as anterior gradient homolog 2 were identified. Protein supplementation resulted in significant differential regulation of 64 genes; affected functions included protein synthesis, cellular function and maintenance. It increased cell metabolism, evident from the high number of non-coding RNA and the increased synthesis of ribosomal proteins. It regulated immune responses, through T-cell activation and proliferation. The up-regulation of transcription factor forkhead box P1 in unsupplemented, parasitised hosts may be indicative of a delayed immune response in these animals.This study provides the first evidence for nutritional regulation of genes related to immunity to nematodes at the site of parasitism, during expulsion. Additionally it reveals genes induced following secondary parasite challenge in lactating mammals, not previously associated with parasite expulsion. This work is a first step towards defining disease predisposition, identifying markers for nutritional imbalance and developing sustainable measures for parasite control in domestic mammals

Glutamine supplementation

Intravenous glutamine supplementation is standard care when parenteral nutrition is given for critical illness. There are data of a reduced mortality when glutamine supplementation is given. In addition, standard commercial products for parenteral nutrition do not contain any glutamine due to glutamine instability in aqueous solutions. For the majority of critical ill patients who are fed enterally, the available evidence is insufficient to recommend glutamine supplementation. Standard formulation of enteral nutrition contains some glutamine: 2-4 g/L. However, this dose is insufficient to normalize glutamine plasma concentration

Glutamine-enriched enteral nutrition increases in vitro interferon-gamma production but does not influence the in vivo specific antibody response to KLH after severe trauma. A prospective, double blind, randomized clinical study.

20) were sensitized with Keyhole Limpet Hemocyanin (KLH) within 12 h after trauma (17 GLN group). Healthy volunteers served as controls (HV, n=17). In vitro interferon-gamma (IFN-gamma), IL-4 and IL-10 productions of phytohemagglutinin (PHA)-stimulated PBMCs were determined by ELISA technique. KLH-specific IgG, IgM, IgA, IgG1, IgG2, IgG3, IgG4 and IgE were measured in serum. RESULTS: Both patient groups had a low in vitro (IFN-) production of stimulated PBMCs on d1. On d14, the IFN-gamma production increased significantly in the glutamine group as compared to the controls. IL-4 production was not different between the groups on day 1 (d1). On d14, IL-4 decreased in the control group as compared to the glutamine group. KLH-specific antibodies reached comparable levels in both patients groups and healthy volunteers at d14. CONCLUSIONS: In conclusion, trauma caused a suppressed in vitro cellular immune response presented by a low IFN-gamma production and depressed the IgG and IgM response to KLH directly after trauma. Glutamine increased IFN-gamma production (d14), maintained a normal IL-4 production, but was not acquired for the development of KLH-specific humoral response on d14, in sync suggesting that dietary glutamine supports the restoration of the Type-1 T-lymphocyte responsiveness

Gut Mucosal and Plasma Concentrations of Glutamine: A Comparison between Two Enriched Enteral Feeding Solutions in Critically Ill Patients

BACKGROUND: Addition of glutamine to enteral nutrition formulas is consistently associated with a significant decrease in septic morbidity in critically ill patients, possibly related to the attenuation of gut dysfunction. This pilot study was undertaken to compare the effects of enteral administration of two glutamine-enriched formulas containing either additional free glutamine or glutamine-rich proteins, with a standard solution on plasma and mucosal concentrations of glutamine in patients admitted in the Department of Intensive Care. METHODS: Following randomization, glutamine concentration was determined in endoscopically sampled duodenal biopsies and plasma, before and after a 7-day period of continuous administration of the designated solution. RESULTS: The mucosal concentration of glutamine increased in the duodenal biopsies sampled from patients randomized to the solution containing the glutamine-rich proteins (from 3.6 +/- 2.2 to 6.7 +/- 5.2 micro-mol/g protein), but not from the others. There were no differences between the 3 groups in the plasma concentrations of glutamine, which remained stable over time. CONCLUSION: The source of supplemental glutamine can influence gut mucosal glutamine concentrations, suggesting differences in its availability or utilization